Leukemia and ABC Transporters.

Leukemia and ABC Transporters. Adv Cancer Res. 2015;125:171-96 Authors: Fukuda Y, Lian S, Schuetz JD Abstract Acute myeloid leukemia (AML) is a heterogeneous disease caused by aberrant proliferation and/or differentiation of myeloid progenitors. However, only ~65% of AML patients respond to induction chemotherapy and the overall survival rate for AML remains low (~24% for 5-year survival). The conventional view suggests that ATP-binding cassette (ABC) transporters contribute to treatment failure due to their drug-effluxing capabilities. This might be overly simplistic. Some ABC transporters export endogenous substrates that have defined roles in normal hematopoietic progenitors. It is conceivable that these substances also provide an advantage to leukemic progenitors. This review will highlight how certain endogenous substrates impact normal hematopoietic cells and suggest that ABC transporters facilitate export of these substances to affect both normal hematopoietic and leukemic progenitors. For example, the ability to export certain endogenous ligands may facilitate leukemogenesis by modifying leukemic progenitor cell proliferation or survival. If so, the addition of ABC transporter inhibitors to traditional chemotherapy might improve therapeutic efficacy by not just increasing intracellular drug accumulation but also blocking the beneficial effects ABC transporter ligands have on cell survival. PMID: 25640270 [PubMed - in process]
Source: Advances in Cancer Research - Category: Cancer & Oncology Authors: Tags: Adv Cancer Res Source Type: research

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ConclusionAround 40% of patients had fever at the time of presentation, and 31% had documented infections. Baseline infections led to increase in induction mortality. We would like to propose that infection at baseline is to be considered as one of the potential variables in the predictive scoring system for induction mortality in developing countries.
Source: Supportive Care in Cancer - Category: Cancer & Oncology Source Type: research
AbstractBackground Patients with haematological malignancies are at high risk of invasive fungal infections. However, there is a lack of information about the utilisation of the recommended Australian antifungal prophylaxis guidelines in haematology outpatients.Objective To assess the impact of a weekly pharmacist review of high-risk adult haematology outpatients on the utilisation of appropriate antifungal prophylaxis.Setting Outpatient cancer centre, tertiary referral hospital in Sydney, Australia.Method A 3-month pre-and post-interventional study was conducted. A retrospective audit was conducted to obtain baseline util...
Source: International Journal of Clinical Pharmacy - Category: Drugs & Pharmacology Source Type: research
ConclusionCytarabine stability is higher in AML than in CTRL samples. The absence of correlation betweent1/2IVdeg and AUCIVlast in AML samples suggests that in vitro cytarabine degradation in AML is complex. These results open perspectives including the evaluation of the clinical relevance and the involved molecular mechanisms.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
ConclusionPotentially clinically relevant DDI effects with CYP3A4 inducers and moderate and strong inhibitors co-administered with ivosidenib were predicted. Considering the challenges of conducting clinical DDI studies in patients, this PBPK approach is valuable in ivosidenib DDI risk assessment and management.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Genetic mutations can predict favorable or unfavorable prognosis of AML patients. Allo stem cell transplantation can provide benefits for AML patients with bad genetic mutations. AbstractTo explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next ‐generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction che...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
ong The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling path...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial. METHODS: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017). RESULTS: Overall, 367 patients received...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
ConclusionTogether these results confirm that glasdegib  + LDAC treatment (vs. LDAC alone) is associated with a significant survival benefit in patients with newly diagnosed AML, and that variability in glasdegib doses (e.g., for dose reductions) and exposures do not compromise the survival benefit of glasdegib 100 mg QD.Clinical Trial numberNCT01546038.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
CONCLUSION: Entosplentib with intensive chemotherapy was well tolerated in AML patients. Improved survival was observed in patients with HOXA9/MEIS1 overexpression, contrasting published data demonstrating poor survival in such patients. A randomized study will be necessary to determine whether entospletinib was a mediator this observation. PMID: 32820015 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
In conclusion, a comprehensive molecular profile for NK-AML allows for the identification of genetic lesions associated to different clinical outcomes and the selection of the most appropriate and effective treatment strategies, including stem cell transplantation and targeted therapies.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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